Mester J C, Highlander S L, Osmand A P, Glorioso J C, Rouse B T
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996-0845.
J Virol. 1990 Nov;64(11):5277-83. doi: 10.1128/JVI.64.11.5277-5283.1990.
Herpes simplex virus (HSV) envelope glycoproteins are the prime targets of adaptive antiviral immunity. Previous investigation identified a protective, neutralizing, glycoprotein B1 (gB-1)-reactive monoclonal antibody (MAb B6) and localized the linear epitope recognized by the MAb to residue 84 of gB-1. Three overlapping peptides (two 20-mers and one 18-mer), together spanning amino acids 63 to 110 of the wild-type sequence of gB-1, were synthesized and analyzed for their ability to stimulate immunity which cross-reacts with HSV-1. All stimulated some level of response. Two peptides, the gB 18-mer and 20.1-mer, were recognized by MAb B6 and HSV-immune antibody but were unable to stimulate virus-neutralizing antibody or serum able to protect against zosteriform spread in vivo. The 20.2-mer peptide, however, which was not recognized by MAb B6 or HSV-generated immune antibody, stimulated the production of neutralizing antibody and serum able to protect against zosteriform spread. Immunization with all of the peptides was able to enhance viral clearance of a low dose of HSV-1 in an ear challenge model and induce antibody reactive in antibody-dependent complement-mediated lysis of HSV-1-infected cells in vitro. These results are the first report of HSV immunity induced by peptides corresponding to gB and indicate that the best immunogen, in terms of stimulating neutralizing antiserum able to protect in vivo against HSV-1, was a peptide not recognized by HSV-immune mechanisms or by the MAb used to localize it.
单纯疱疹病毒（HSV）包膜糖蛋白是适应性抗病毒免疫的主要靶点。先前的研究鉴定出一种具有保护性、中和性的糖蛋白B1（gB-1）反应性单克隆抗体（单克隆抗体B6），并将该单克隆抗体识别的线性表位定位到gB-1的第84位残基。合成了三个重叠肽（两个20肽和一个18肽），它们共同覆盖gB-1野生型序列的第63至110位氨基酸，并分析了它们刺激与HSV-1交叉反应的免疫的能力。所有肽都刺激了一定程度的反应。两个肽，即gB 18肽和20.1肽，可被单克隆抗体B6和HSV免疫抗体识别，但无法刺激病毒中和抗体或能在体内预防带状疱疹样扩散的血清产生。然而，20.2肽不能被单克隆抗体B6或HSV产生的免疫抗体识别，却能刺激中和抗体和能预防带状疱疹样扩散的血清产生。在耳部攻击模型中，用所有这些肽进行免疫能够增强低剂量HSV-1的病毒清除率，并在体外诱导抗体在抗体依赖性补体介导的HSV-1感染细胞裂解中产生反应。这些结果是关于由与gB对应的肽诱导的HSV免疫的首次报道，表明就刺激能够在体内保护免受HSV-1感染的中和抗血清而言，最佳免疫原是一种既不被HSV免疫机制也不被用于定位它的单克隆抗体识别的肽。
